Evolution's footprints in human genome precisely tracked using new approach

Date:

January 8, 2010

Source:

Broad Institute of MIT and Harvard

Summary:

Fossils may provide tantalizing clues to human history but they also lack some vital information, such as revealing which pieces of human DNA have been favored by evolution because they confer beneficial traits -- resistance to infection or the ability to digest milk, for example. Now, researchers describe a method for pinpointing these preferred regions that offers greater precision and resolution than ever before, and the possibility of deeply understanding both our genetic past and present.

Share:

Total shares:

FULL STORY

Researchers have developed a new method for pinpointing pieces of human DNA have been favored by evolution within the human genome. The technique offers greater precision and resolution than ever before.

Credit: iStockphoto

Researchers have developed a new method for pinpointing pieces of human DNA have been favored by evolution within the human genome. The technique offers greater precision and resolution than ever before.

Credit: iStockphoto

Fossils may provide tantalizing clues to human history but they also lack some vital information, such as revealing which pieces of human DNA have been favored by evolution because they confer beneficial traits -- resistance to infection or the ability to digest milk, for example. These signs can only be revealed through genetic studies of modern humans and other related species, though the task has proven difficult.

Now, in a paper appearing in the January 7 edition of Science Express, researchers describe a method for pinpointing these preferred regions within the human genome that offers greater precision and resolution than ever before, and the possibility of deeply understanding both our genetic past and present.

"It's clear that positive natural selection has been a critical force in shaping the human genome, but there are remarkably few examples that have been clearly identified," said senior author Pardis Sabeti, an associate member of the Broad Institute of Harvard and MIT and an assistant professor of organismic and evolutionary biology at Harvard University. "The method we've developed makes it possible to zero in on individual genes as well as the specific changes within them that are driving important evolutionary changes."

Positive natural selection is a process in which advantageous traits become more common in a population. That is because these traits boost an individual's chances of survival and reproduction, so they are readily passed on to future generations. Identifying such traits -- and the genes underlying them -- is a cornerstone of current efforts to dissect the biological history of the human species as well as the diseases that threaten human health today.

"In the human genome, positive natural selection leaves behind very distinctive signals," said co-first author Sharon Grossman, a research assistant at Harvard University and the Broad Institute. Yet earlier methods for detecting these signals are limited, highlighting relatively large chunks of the genome that are hundreds of thousands to millions of genetic letters or "bases" in length, and that can contain many genes.

Of the hundreds of these large genomic regions thought to be under positive natural selection in humans, only a handful have so far been winnowed to a precise genetic change. "Finding the specific genetic changes that are under selection can be like looking for a needle in a haystack," said Grossman.

Sabeti, Grossman and their colleagues wondered if there might be a way to enhance this genomic search. Because existing methods for detecting natural selection each measure distinct genomic features, the researchers predicted that an approach that combines them together could yield even better results.

After some initial simulations to test their new method, the research team applied it to more than 180 regions of the human genome that are thought to be under recent positive selection, yet in most cases, the specific gene or genetic variant under selection is unknown.

The researchers' method, called "Composite of Multiple Signals" or CMS, enabled them to dramatically narrow the size of the candidate regions, reducing them from an average of eight genes per region to one. Moreover the number of candidate genetic changes was reduced from thousands to just a handful, helping the researchers tease out the needles from the haystack.

"The list of genes and genetic loci we identified includes many intriguing candidates to follow up," said co-first author Ilya Shylakhter, a computational biologist at the Broad Institute and Harvard University. "For example, a number of genes identified are involved in metabolism, skin pigmentation and the immune system."

In some cases, the researchers were able to identify a specific genetic change that is the likely focal point of natural selection. For example, a variation in a gene called protocadherin 15, which functions in sensory perception, including hearing and vision, appears to be under selection in some East Asian populations. Several other genes involved in sensory perception also appear to be under selection in Asia. In addition, the team uncovered strong evidence of selection in East Asians at a specific point within the leptin receptor gene, which is linked to blood pressure, body mass index and other important metabolic functions.

Interestingly, the researchers also localized signals to regions outside of genes, suggesting that they function not by altering gene structure per se, but by changing how certain genes are turned on and off.

While the findings in the Science paper offer a deep glimpse of evolution's handiwork, the researchers emphasize that further studies of individual genetic variations, involving experiments that explore how certain genetic changes influence biological function, are necessary to fully dissect the role of natural selection and its impact on human biology.

"This method allows us to trace evolution's footprints with a much finer level of granularity than before, but it's one piece of a much larger puzzle," said Sabeti. "As more data on human genetic variation becomes available in the coming years, an even more detailed evolutionary picture should emerge."

Story Source:

The above post is reprinted from materials provided by Broad Institute of MIT and Harvard. The original item was written by Nicole Davis, Broad Institute of Harvard and MIT. Note: Materials may be edited for content and length.

July 28, 2015  Scientists write that sea-level rise (3.4 mm/yr) is faster in the Chesapeake Bay region than any other location on the Atlantic coast of North America, and twice the global average (1.7 mm/yr). They ... read more

July 28, 2015  The light-sensing molecules that tell plants whether to germinate, when to flower and which direction to grow to seek more sunlight were inherited millions of years ago from ... read more

July 27, 2015  The Viking hit-and-run raids on monastic communities such as Lindisfarne and Iona were the most infamous result of burgeoning Scandinavian maritime prowess in the closing years of the Eighth ... read more

July 20, 2015  For the first time, advanced technologies made it possible to read parts of a damaged scroll that is at least 1,500 years old, discovered inside the Holy Ark of the synagogue ... read more

July 23, 2015  New research reveals that some of the earliest civilizations in the Middle East and the Fertile Crescent may have been affected by abrupt climate change. These findings show ... read more

July 23, 2015  Measurements of iron speciation in ancient rocks were used to construct the chemistry of ancient oceans. Analysis suggests that it took less oxygen than previously thought to ... read more

July 22, 2015  Animal populations on islands tend to develop weird traits over time, becoming big or small or losing the ability to fly. One less-studied pattern of evolution on islands is ... read more

June 15, 2015  In a study that twists nature's arm to gain clues into the varied functions of the bacterial genome, researchers utilize a precision scalpel to excise target genomic regions that are expendable. ... read more

Feb. 14, 2013  A pair of studies sheds new light on genetic variation that may have played a key role in human evolution. The study researchers used an animal model to study a gene variant that could have helped ... read more

Dec. 5, 2012  The National Geographic Society has announced the next phase of its Genographic Project -- the multiyear global research initiative that uses DNA to map the history of human migration. Building on ... read more